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Novel metabolic role for BDNF in pancreatic β-cell insulin secretion

Author

Listed:
  • Gianluca Fulgenzi

    (CCR, NCI, NIH)

  • Zhenyi Hong

    (CCR, NCI, NIH)

  • Francesco Tomassoni-Ardori

    (CCR, NCI, NIH)

  • Luiz F. Barella

    (Laboratory of Bioorganic Chemistry, NIDDK, NIH)

  • Jodi Becker

    (CCR, NCI, NIH)

  • Colleen Barrick

    (CCR, NCI, NIH)

  • Deborah Swing

    (CCR, NCI, NIH)

  • Sudhirkumar Yanpallewar

    (CCR, NCI, NIH)

  • Brad St Croix

    (CCR, NCI, NIH)

  • Jürgen Wess

    (Laboratory of Bioorganic Chemistry, NIDDK, NIH)

  • Oksana Gavrilova

    (Mouse Metabolism Core Laboratory, NIDDK, NIH)

  • Lino Tessarollo

    (CCR, NCI, NIH)

Abstract

BDNF signaling in hypothalamic circuitries regulates mammalian food intake. However, whether BDNF exerts metabolic effects on peripheral organs is currently unknown. Here, we show that the BDNF receptor TrkB.T1 is expressed by pancreatic β-cells where it regulates insulin release. Mice lacking TrkB.T1 show impaired glucose tolerance and insulin secretion. β-cell BDNF-TrkB.T1 signaling triggers calcium release from intracellular stores, increasing glucose-induced insulin secretion. Additionally, BDNF is secreted by skeletal muscle and muscle-specific BDNF knockout phenocopies the β-cell TrkB.T1 deletion metabolic impairments. The finding that BDNF is also secreted by differentiated human muscle cells and induces insulin secretion in human islets via TrkB.T1 identifies a new regulatory function of BDNF on metabolism that is independent of CNS activity. Our data suggest that muscle-derived BDNF may be a key factor mediating increased glucose metabolism in response to exercise, with implications for the treatment of diabetes and related metabolic diseases.

Suggested Citation

  • Gianluca Fulgenzi & Zhenyi Hong & Francesco Tomassoni-Ardori & Luiz F. Barella & Jodi Becker & Colleen Barrick & Deborah Swing & Sudhirkumar Yanpallewar & Brad St Croix & Jürgen Wess & Oksana Gavrilov, 2020. "Novel metabolic role for BDNF in pancreatic β-cell insulin secretion," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15833-5
    DOI: 10.1038/s41467-020-15833-5
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